Русский 
English Molecular dynamic model of NDC80 complex interaction with a microtubule
Background
In the process of cell division, kinetochores interact with microtubules, resulting in the separation of sister chromosomes. One of the key elements kinetochore-microtubule attachment is the NDC80 protein complex.
Aims
Establish the dynamic and structural properties of the NDC80 complex and its interaction with the microtubule using molecular modeling methods.
Methods
We used coarse-grained explicit solvent molecular dynamics calculations to simulate the behavior of the NDC80 complex dissociation under applied force. In our MARTINI model, one coarse-grain particle replaced a group of, on average, 4 heavy atoms with hydrogen atoms associated with them, which allowed us to get rid of the fastest molecular degrees of freedom and, accordingly, increase the integration step of the molecular dynamics equations. This approach makes it possible to accelerate molecular dynamics calculations up to 2 orders of magnitude. As a result, MARTINI 3 coarse-grain force-field which is optimal for protein simulation allowed us to study the process of NDC80 complex dissociation induced by force at almost atomic resolution at the microsecond timescale. For molecular dynamics calculations we used the Gromacs software package.
Results
Computational experiments of the force-induced dissociation of the NDC80 complex with the application of forces of 9 pN, 16 pN, and 25 pN along the microtubule axis towards its plus and minus ends were carried out. These experiments have shown that the binding force is higher when a force is applied towards the plus-end, compared to movement towards the minus-end. This asymmetry of diffusion of the NDC80 complex along a microtubule under the action of a mechanical force may arise due to the initial orientation of the supercoiled section at an angle toward the plus-end of the microtubule. Besides, the contact area between the NDC80 and the microtubule significantly expands upon relaxation of the complex due to the formation of additional contacts of tubulin with Nuf2 protein, reinforcing the asymmetry of the NDC80 complex motion along the microtubule under the influence of mechanical force.
Conclusions
Our study offers an explanation of the asymmetry of diffusion of the NDC80 complex along a microtubule under force, recently experimentally discovered by the group of prof. F.I. Ataullakhanov and co-authors.
Funding
This work was supported by the Interdisciplinary Scientific and Educational School of Moscow University “Photonic and Quantum Technologies. Digital Medicine”.